Genomic characterization of invasive typhoidal and non-typhoidal Salmonella in southwestern Nigeria

Abstract

Background Salmonellosis causes significant morbidity and mortality in Africa. Information on lineages of invasive Salmonella circulating in Nigeria is sparse. Methods Salmonella enterica isolated from blood (n = 60) and cerebrospinal fluid (CSF, n = 3) between 2016 and 2020 from five tertiary hospitals in southwest Nigeria were antimicrobial susceptibility-tested and Illumina-sequenced. Genomes were analysed using publicly-available bioinformatic tools. Results Isolates and sequence types (STs) from blood were S. Typhi [ST1, n = 1 and ST2, n = 43] and invasive non-typhoidal Salmonella (iNTS) (S. Enteritidis [ST11, n = 7], S. Durham [ST10, n = 2], S. Rissen [ST8756, n = 2], S. Chester [ST2063, n = 1], S. Dublin [ST10, n = 1], S. Infantis [ST603, n = 1], S. Telelkebir [ST8757, n = 1] and S. Typhimurium [ST313, n = 1]). S. Typhi ST2 (n = 2) and S. Adabraka ST8757 (n = 1) were recovered from CSF. Most S. Typhi belonged to genotype 3.1.1 (n = 44), carried an IncY plasmid, had several antibiotic resistance genes (ARGs) including blaTEM-1 (n = 38), aph(6)-Id (n = 32), tet(A) (n = 33), sul2 (n = 32), dfrA14 (n = 30) as well as quinolone resistance-conferring gyrA_S83Y single-nucleotide polymorphisms (n = 37). All S. Enteritidis harboured aph(3”)-Ib, blaTEM-1, catA1, dfrA7, sul1, sul2, tet(B) genes, and a single ARG, qnrB19, was detected in S. Telelkebir. Typhoidal toxins cdtB, pltA and pltB were detected in S. Typhi, Rissen, Chester, and Telelkebir. Conclusion Most invasive salmonelloses in southwest Nigeria are vaccine-preventable infections due to multidrug-resistant, West African dominant S. Typhi lineage 3.1.1. Invasive NTS serovars, including some harbouring typhoidal toxin or resistance genes, represented a third of the isolates emphasizing the need for better diagnosis and surveillance.

Global diversity and antimicrobial resistance of typhoid fever pathogens: insights from 13,000SalmonellaTyphi genomes

“…However, overall, bla CTX-M-15 IncY plasmids were rare (n=1 to 4 genomes) in all genotype backgrounds except 4.3.1.1.P1 (total n=655), suggesting that the IncY bla CTX-M-15 plasmid has not been stably maintained in other Typhi lineages (see Table 3). IncY plasmids were also identified in a single genotype 2.3.3 organism isolated in the UK in 1989 associated with travel to Pakistan (carrying catA1, tetA(B)); and in a sublineage of IncHI1-negative 3.1.1 genomes from Nigeria carrying bla TEM-1D , dfrA14, sul2, tetA(A), as has been recently reported (Ikhimiukor et al, 2022a;International Typhoid Consortium et al, 2016). Other examples of ESBL carriage in Typhi genomes appear to represent isolated events (1 or 2 genomes per ESBL/plasmid or ESBL/genotype combination, see Table 3), except for a sublineage of 4.3.1.2.1 from India carrying bla SHV-12 in a IncX3 plasmid backbone.…”

“…Most of these data come from the Typhoid Fever Surveillance in Africa Programme (TSAP) genomics report (Park et al, 2018) and a study of typhoid in Abuja and Kano in Nigeria (International Typhoid Consortium et al, 2016), which showed that in the period 2010-2013, 3.1.1 dominated in Nigeria and nearby Ghana and Burkina Faso, whereas 2.3.2 dominated in The Gambia and neighbouring Senegal and Guinea Bissau (Park et al, 2018). Here, we find that additional data from travel cases and recent Nigerian national surveillance (Ikhimiukor et al, 2022a) suggest that these patterns reflect long-established and persisting populations in the Western African region (see Figures S1b and S3): 3.1.1 was detected from Benin (2002Benin ( -2009n=4/4), Burkina Faso (2006-2013n=11/17), Cote d'Ivoire (2006n=4/4) -2014n=25/28), Ghana (2010n=25/28), Ghana ( -2018n=9/109), Guinea Bissau (2012-2013n=2/3), Mali (1999n=2/3), Mali ( -2018n=3/5), Niger (1990n=3/5), Niger ( -1999n=2/4), Nigeria (1984n=2/4), Nigeria ( -2002n=4/192) The Americas Strikingly, Central American isolates were dominated by 2.3.2 (55%, [95% CI, 45.2-64.8%] n= 55/100), which was also common in Western Africa (13.9%, [95% CI, 9.7-18.0%]; n=37/266) (Figure 1a). Little has been reported about Typhi populations from this region previously, and the genomes collated here were almost exclusively novel ones contributed via the US CDC and isolated between 2016 and 2019.…”

“…Overall, there were 36 countries with ≥20 genomes (total n=12,409 genomes, 95.7%) and 21 countries with ≥100 genomes (n=11,761 genomes, 90.7%) (see Table S4). Countries with the most genomes available (n≥100 each) were mainly those where local surveillance studies have utilised WGS for isolate characterisation (India (Britto et al, 2020;da Silva et al, 2022), Bangladesh (Rahman et al, 2020;da Silva et al, 2022), Nepal (Britto et al, 2018;Thanh et al, 2016a), Pakistan (da Silva et al, 2022, Cambodia (Kuijpers et al, 2017;Thanh et al, 2016b), Laos (Wong et al, 2015), Vietnam (Holt et al, 2011a), Kenya (Kariuki et al, 2021(Kariuki et al, , 2010, Malawi (Feasey et al, 2015), Zimbabwe (Mashe et al, 2020;Thilliez et al, 2022), Ghana (Park et al, 2018), Nigeria (Ikhimiukor et al, 2022a;International Typhoid Consortium et al, 2016), Chile (Maes et al, 2022), Samoa (Sikorski et al, 2022)); plus South Africa, the Philippines (Lagrada et al, 2022), United Kingdom and United States, where Typhi isolates are sequenced as part of national surveillance programmes.…”

“…The genotyping framework, together with functionality for identifying AMR determinants and plasmid replicons, and generating clustering-based trees, is available within the online genomic epidemiology platform Typhi Pathogenwatch (Argimon et al, 2021). This system is designed to facilitate genomic surveillance and outbreak analysis for Typhi, including contextualisation with global public data, by public health and research laboratories (Argimón et al, 2021;Ikhimiukor et al, 2022a;Lagrada et al, 2022) without requiring major investment in computational infrastructure or specialist bioinformatics training.…”

Establishing a national reference laboratory for antimicrobial resistance using a whole-genome sequencing framework: Nigeria’s experience

“…Moreover, our WGS surveillance found a sublineage of 3.1.1 strains that carry an IncY multi-drug resistance plasmid (Fig. 3) [45]. In addition to providing valuable information about Typhi epidemiology in Nigeria, genomic surveillance has made it possible to correctly subtype invasive non-typhoidal Salmonella, all of which are submitted by sentinels to the reference laboratory with no serovar information.…”